飯匙倩神經毒對箭毒在天竺鼠大腦皮質神經膜之結合無競爭作用

Abstract

從蛇類毒液中分離之神經毒，依其在神經肌肉連會(Neuromuscular junction)上之作用可分成： 1．突觸後神經毒(Postsynaptic Neurotoxin) 此種神經毒作用於神經肌肉連會上之突觸後膜(post-synaptic membrane)□膜上之它古丁類膽素受體(Nicotinic Cholinergic receptor)發生結合阻止了乙醯膽鹼(Acetylchoeine)□其受體之結合，此作用之形式與箭毒相似。此種類型之神經毒有：雨傘節神經毒甲(α-Bungarotoxin)和眼睛蛇神經毒(Cobra Neurotoxin)。 2．突觸前神經毒(presynaptic Neurotoxin) 此種神經毒作用於神經肌肉連會上之突觸前膜(Presynaptic membrane)，影響乙醯膽鹼之釋放。如：雨傘節神經毒乙(β-Bungarotoxin)。 在神經系統中，如中樞神經及交感神經節中這種突觸後神經毒會□之結合，而且此種結合亦受各種膽素藥物(Cholinergic drugs)之影響．故一般均假設此結合體即乙醯膽鹼受體(Acetylcholine receptor)，但在交感神經節中(Sympathatic ganglia),有以免疫的技術證明其中此種神經毒結合之蛋白質分子非乙醯膽鹼之受體。 在本報告中以箭毒素(H3-tubocurarine)□天竺鼠大腦皮質分離之突觸小體(Synaptosome)進行結合實驗.發現有非協同(noncooperative)式之結合，也可測得之結合體只有一種，其解離係數(dissociation constant)則介於0.4×10-6M與1.67×10-6M之間．結合體(Bingding Site)之濃度則介於每毫克蛋白質中有0.2×10-9mol至1.42×10-9mol，又箭毒素(tubocurarine)的結合在分離出之各細胞成分間之分佈□突觸小體細胞膜之分佈非常相似．但是此種結合卻不受眼鏡蛇神經毒之影響．使我們猜測突觸後神經毒在大腦皮質中之結合體也許也非乙醯膽鹼受體，如其在交感神經節中之情形．但由於箭毒素之結合體並未證明為乙醯膽鹼之受體．故對此種結論仍需保留．

Cobra neurotoxin and α-Bungarotoxin produce neuromuscular blockade by binding to postsynaptic receptor for acetylcholine and they have been used in attempts to characterize acetylcholine receptor in muscle and in the electric organ of Electrophorus and Torpedo. However, recently it has been shown that the binding protein for α-bungarotoxin in ganglia is not acetylcholine receptor. In this study, nicotinic antagonist H3- tubocurarine was found to bind to synaptosomes from cerebral cortex of guinea pig in a non-cooperative manner. Only one binding site for tubocurarine with dissociation constant between 0.4 × 10-6M to 1.67 × 10-6M was detected. The concentration of binding site in synaptosomes is between 0.2 × 10-9mo1/mg protein to 1.42 × 10-9mol/mg protein. Subcellular distribution of tubocurarine binding roughly parallels the distribution of synaptosomal membrane. But cobra neurotoxin, even at a concentration as high as 1 mM, has no effect on the binding of tubocurarine to synaptosome.